The Role of Astrocytes in Neuroprotection After Brain Stroke: Potential in Cell Therapy

Overview

Journal Front Mol Neurosci

Specialty Molecular Biology

Date 2017 Apr 20

PMID 28420961

Citations 119

Authors

Andrea Becerra-Calixto

Gloria P Cardona-Gomez

Affiliations

Soon will be listed here.

Abstract

Astrocytes are commonly involved in negative responses through their hyperreactivity and glial scar formation in excitotoxic and/or mechanical injuries. But, astrocytes are also specialized glial cells of the nervous system that perform multiple homeostatic functions for the survival and maintenance of the neurovascular unit. Astrocytes have neuroprotective, angiogenic, immunomodulatory, neurogenic, and antioxidant properties and modulate synaptic function. This makes them excellent candidates as a source of neuroprotection and neurorestoration in tissues affected by ischemia/reperfusion, when some of their deregulated genes can be controlled. Therefore, this review analyzes pro-survival responses of astrocytes that would allow their use in cell therapy strategies.

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References

Gibbs M, Anderson D, Hertz L . Inhibition of glycogenolysis in astrocytes interrupts memory consolidation in young chickens. Glia. 2006; 54(3):214-22. DOI: 10.1002/glia.20377. View

Eng L, Ghirnikar R, Lee Y . Glial fibrillary acidic protein: GFAP-thirty-one years (1969-2000). Neurochem Res. 2000; 25(9-10):1439-51. DOI: 10.1023/a:1007677003387. View

Gutierrez-Vargas J, Munera A, Cardona-Gomez G . CDK5 knockdown prevents hippocampal degeneration and cognitive dysfunction produced by cerebral ischemia. J Cereb Blood Flow Metab. 2015; 35(12):1937-49. PMC: 4671113. DOI: 10.1038/jcbfm.2015.150. View

Sofroniew M, Vinters H . Astrocytes: biology and pathology. Acta Neuropathol. 2009; 119(1):7-35. PMC: 2799634. DOI: 10.1007/s00401-009-0619-8. View

Li L, Lundkvist A, Andersson D, Wilhelmsson U, Nagai N, Pardo A . Protective role of reactive astrocytes in brain ischemia. J Cereb Blood Flow Metab. 2007; 28(3):468-81. DOI: 10.1038/sj.jcbfm.9600546. View

Le Bras B, Barallobre M, Homman-Ludiye J, Ny A, Wyns S, Tammela T . VEGF-C is a trophic factor for neural progenitors in the vertebrate embryonic brain. Nat Neurosci. 2006; 9(3):340-8. DOI: 10.1038/nn1646. View

Cross M, Claesson-Welsh L . FGF and VEGF function in angiogenesis: signalling pathways, biological responses and therapeutic inhibition. Trends Pharmacol Sci. 2001; 22(4):201-7. DOI: 10.1016/s0165-6147(00)01676-x. View

Hsuan Y, Lin C, Chang C, Lin M . Mesenchymal stem cell-based treatments for stroke, neural trauma, and heat stroke. Brain Behav. 2016; 6(10):e00526. PMC: 5064338. DOI: 10.1002/brb3.526. View

Kaczor P, Rakus D, Mozrzymas J . Neuron-astrocyte interaction enhance GABAergic synaptic transmission in a manner dependent on key metabolic enzymes. Front Cell Neurosci. 2015; 9:120. PMC: 4391237. DOI: 10.3389/fncel.2015.00120. View

10.

Benarroch E . Neuron-astrocyte interactions: partnership for normal function and disease in the central nervous system. Mayo Clin Proc. 2005; 80(10):1326-38. DOI: 10.4065/80.10.1326. View

11.

Rostworowski M, Balasingam V, Chabot S, Owens T, Yong V . Astrogliosis in the neonatal and adult murine brain post-trauma: elevation of inflammatory cytokines and the lack of requirement for endogenous interferon-gamma. J Neurosci. 1997; 17(10):3664-74. PMC: 6573669. View

12.

Zeng X, Sun X, Gao L, Fan Y, Ding J, Hu G . Aquaporin-4 deficiency down-regulates glutamate uptake and GLT-1 expression in astrocytes. Mol Cell Neurosci. 2006; 34(1):34-9. DOI: 10.1016/j.mcn.2006.09.008. View

13.

Brown A, Sickmann H, Fosgerau K, Lund T, Schousboe A, Waagepetersen H . Astrocyte glycogen metabolism is required for neural activity during aglycemia or intense stimulation in mouse white matter. J Neurosci Res. 2004; 79(1-2):74-80. DOI: 10.1002/jnr.20335. View

14.

Suzumura A, Takeuchi H, Zhang G, Kuno R, Mizuno T . Roles of glia-derived cytokines on neuronal degeneration and regeneration. Ann N Y Acad Sci. 2006; 1088:219-29. DOI: 10.1196/annals.1366.012. View

15.

Gleichman A, Carmichael S . Astrocytic therapies for neuronal repair in stroke. Neurosci Lett. 2013; 565:47-52. DOI: 10.1016/j.neulet.2013.10.055. View

16.

Kitchen P, Day R, Taylor L, Salman M, Bill R, Conner M . Identification and Molecular Mechanisms of the Rapid Tonicity-induced Relocalization of the Aquaporin 4 Channel. J Biol Chem. 2015; 290(27):16873-81. PMC: 4505433. DOI: 10.1074/jbc.M115.646034. View

17.

Morganti-Kossmann M, Satgunaseelan L, Bye N, Kossmann T . Modulation of immune response by head injury. Injury. 2007; 38(12):1392-400. DOI: 10.1016/j.injury.2007.10.005. View

18.

Herx L, Rivest S, Yong V . Central nervous system-initiated inflammation and neurotrophism in trauma: IL-1 beta is required for the production of ciliary neurotrophic factor. J Immunol. 2000; 165(4):2232-9. DOI: 10.4049/jimmunol.165.4.2232. View

19.

Posada-Duque R, Lopez-Tobon A, Piedrahita D, Gonzalez-Billault C, Cardona-Gomez G . p35 and Rac1 underlie the neuroprotection and cognitive improvement induced by CDK5 silencing. J Neurochem. 2015; 134(2):354-70. PMC: 4491027. DOI: 10.1111/jnc.13127. View

20.

Mori T, Buffo A, Gotz M . The novel roles of glial cells revisited: the contribution of radial glia and astrocytes to neurogenesis. Curr Top Dev Biol. 2005; 69:67-99. DOI: 10.1016/S0070-2153(05)69004-7. View